Thiophenes, acylation from carbonyl compounds

The Gewald synthesis can be performed on a solid support. Treatment of resin-bound nitrile 559 with carbonyl compounds and sulfur gives resin-bound aminothiophenes 560. Acylation and removal of the resin provide thiophenes 561 (Scheme 88) <2001TL7181>. The same resin-bound nitrile 559 reacts under MW irradiation to give 560 <2004S3055>. MW-assisted synthesis of 2-A -acylthiophenes 563 from 562 on a solid support has also been reported <2003SL63>. 

Analysis of the above methods for the synthesis of thienothiophenes and their analogues based on thiophene derivatives demonstrates that mono- and dibromo-substituted thiophenes are most often successfully used as the starting compounds. It should be noted that intramolecular cyclization of compounds derived from the above-mentioned thiophenes serves as the key step. In this step, vicinal carbonyl functions (generally, formyl or acyl) interact with fragments containing an activated methylene group. 

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